Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy of Oral Azacitidine Plus Best Supportive Care as Maintenance Therapy in Subjects With Acute Myeloid Leukemia in Complete Remission (QUAZAR AML-001)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01757535
Recruitment Status : Active, not recruiting
First Posted : December 31, 2012
Last Update Posted : July 19, 2019
Sponsor:
Information provided by (Responsible Party):
Celgene

Brief Summary:

This study will enroll approximately 460 subjects, aged 55 or older, with a diagnosis of de novo AML (Acute Myeloid Leukemia) or AML secondary to prior myelodysplastic disease or chronic myelomonocytic leukemia (CMML), and who have achieved first Complete remission (CR)/ Complete remission with incomplete blood count recovery (CRi) following induction with or without consolidation chemotherapy.

The study is amended to include an Extension Phase (EP). The EP allows subjects who are currently receiving oral azacitidine and who are demonstrating clinical benefit as assessed by the Investigator, to continue receive oral azacitidine after unblinding by Sponsor (Celgene Corporation) until the subject meets the criteria for study discontinuation or until oral azacytidine becomes commercially available and reimbursed. In addition, all subjects in the placebo arm and subjects who had been discontinued from the treatment phase (irrespective of randomization arm) and continuing in the Follow-up Phase will be followed for survival in the EP.


Condition or disease Intervention/treatment Phase
Leukemia, Myeloid, Acute Drug: 300 mg Oral Azacitidine Drug: Placebo Phase 3

Detailed Description:

This is an international, multicenter, placebo-controlled, Phase 3 study with a double-blind, randomized, parallel-group design in subjects with de novo AML or AML secondary to prior diagnosis of myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) aged ≥ 55 years, who are in first CR/CRi following induction therapy with or without consolidation chemotherapy. The study consists of 3 phases; the Pre-randomization Phase (Screening Phase), the Treatment Phase, and the Follow-up Phase.

The study is amended to include an Extension Phase (EP). The EP allows subjects who are currently receiving oral azacitidine and who are demonstrating clinical benefit as assessed by the Investigator, to continue receive oral azacitidine after unblinding by Sponsor (Celgene Corporation) until they meet the criteria for study discontinuation or until oral azacitidine becomes commercially available and reimbursed. In addition, all subjects in the placebo arm and subjects who had been discontinued from the treatment phase (irrespective of randomization arm) and continuing in the Follow-up Phase will be followed for survival in the EP.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 472 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Compare Efficacy and Safety of Oral Azacitidine Plus Best-supportive Care Versus Best Supportive Care as Maintenance Therapy in Subjects With Acute Myeloid Leukemia in Complete Remission
Actual Study Start Date : April 24, 2013
Estimated Primary Completion Date : July 15, 2019
Estimated Study Completion Date : December 31, 2021


Arm Intervention/treatment
Experimental: Oral Azacitidine
300mg Oral Azacitidine for the first 14 days of each 28 days treatment cycle
Drug: 300 mg Oral Azacitidine
Maintenance therapy

Placebo Comparator: Placebo
300 mg Placebo for the first 14 days of each 28 days treatment cycle
Drug: Placebo



Primary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: 60 months ]
    Number of participants who survive


Secondary Outcome Measures :
  1. Relapse free survival (RFS) [ Time Frame: 60 months ]
    Number of participants who survive without relapsing

  2. Complete Remission (CR)/Complete Remission with incomplete blood count recovery (CRi) [ Time Frame: 60 months ]
    Time to relapse from Complete Remission (CR)/Complete Remission with incomplete blood count recovery (CRi). Time to relapse from CR/CRi is defined as the interval from the date of randomization to the date of documented relapse after CR or CRi, as defined according to the IWG AML response criteria.

  3. Safety and Tolerability [ Time Frame: 60 months ]
    Number of participants with adverse events

  4. Healthcare Resource Utilization [ Time Frame: 60 months ]
    Effect of oral azacitidine compared with Placebo on healthcare utilization. Healthcare utilization data will be collected as described below: Information on each hospitalization will be collected utilizing a CRF designed specifically for this purpose. Information to be collected will include, but not be limited to, the reason for hospitalization (eg, disease relapse, AML-related illness, treatment-related AE), and days of hospitalization by treatment setting (inpatient, special care unit). Other disease- and treatment-related forms of healthcare utilization will be collected through routine study activities. These include diagnostic procedures and treatment interventions not requiring hospitalization such as those required for AML-related illness, or for treatment-related adverse events. Additionally, information on all concomitant medications and resource use associated with treatment administration for AML will be collected. Healthcare resource utilization information will be

  5. Patient-reported outcomes utilizing the FACIT-Fatigue Scale and the EQ-5D [ Time Frame: 60 months ]
    FACT-F Functional Assessment of Cancer Therapy-Fatigue, EuroQol-5D (EQ-5D) measure of health outcome and 3 additional exploratory questions



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   55 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female subjects ≥ 55 years of age
  2. Newly diagnosed, histologically confirmed de novo AML or AML secondary to prior myelodysplastic disease or CMML (Chronic myelomonocytic leukemia)
  3. First Complete remission (CR)/ Complete remission with incomplete blood count recovery (CRi) with induction therapy + consolidation therapy within 4 months (+/- 7 days of achieving CR or CRi)
  4. Eastern Cooperative Oncology Group (ECOG) performance status - 0, 1, 2, 3

Inclusion Criteria in the Extended Phase of the study:

At the Investigator's discretion and with approval of the sponsor, subjects meeting all of the following eligibility criteria are eligible to enter the extension phase:

  1. All subjects randomized into the oral azacitidine or placebo arm and are continuing in either the Treatment Phase or Follow-up Phase of the CC-486-AML-001 study;

    • Subjects randomized to oral azacitidine treatment arm and continuing in the Treatment Phase demonstrating clinical benefit as assessed by the Investigator are eligible to receive oral azacitidine in the EP;
    • Subjects randomized into placebo arm of the study will not receive oral azacitidine in the EP, but will be followed for survival in the EP;
    • Subjects currently in the in the Follow-up Phase will continue to be followed for survival in the EP;
  2. Subjects who have signed the informed consent for the EP of the study;
  3. Subjects who do not meet any of the criteria for study discontinuation

Exclusion Criteria:

  1. AML with inv(16), t(8;21), t(16;16), t(15;17), or t(9;22) or molecular evidence of such translocations
  2. Prior bone marrow or stem cell transplantation
  3. Have achieved CR/CRi following therapy with hypomethylating agents
  4. Diagnosis of malignant disease within the previous 12 months
  5. Proven Central Nervous System (CNS) leukemia

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01757535


  Show 220 Study Locations
Sponsors and Collaborators
Celgene
Investigators
Layout table for investigator information
Study Director: Ignazia La Torre, MD Celgene Corporation

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT01757535     History of Changes
Other Study ID Numbers: CC-486-AML-001
2012-003457-28 ( EudraCT Number )
First Posted: December 31, 2012    Key Record Dates
Last Update Posted: July 19, 2019
Last Verified: July 2019

Keywords provided by Celgene:
Maintenance therapy
AML
Acute Myeloid Leukemia
oral Azacitidine
best supportive care
complete remission

Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms by Histologic Type
Neoplasms
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors